This project consists of three separate double-blind, active placebo-controlled (diphenhydramine- 12.5 mg) outpatient studies comparing each medication to placebo in one type of population. Treatment included medication and individual counseling twice a week or once a week employing an adaptation of interpersonal psychotherapy (Rounsaville) for 13 weeks. outcome was assessed by drug use (both urine toxicology and self-report), drug craving, mood, and psychosocial functioning (Addiction Severity Index). All subjects were followed up 3, 6, 12 months after active treatment. In the first study, 53 cocaine abusers (ages 21-60) were randomly assigned to receive either fluoxetine-20 mg (n=11), 40 mg (14), 60 mg (12), or placebo (16) daily. All patients also received counseling twice weekly. Although improvement over time was significant for all subjects, there were no significant outcome differences among groups, whether analyzed in terms of medication dose or achieved plasma level (>vs< 100 ng/ml). At follow-up, all groups showed some improvement, with no group differences. In the second study, 45 PCP abusers were randomly assigned to receive either fluoxetine-20 mg daily or placebo, plus counseling twice weekly. Preliminary analyses showed improvement over time but no differences between medication and placebo groups in amount used, urine positives, or mood measures. In the third study, 46 cocaine abusers were randomly assigned to receive either desipramine-300 mg daily or placebo, plus counseling once weekly. Data from this third study have not been analyzed yet.